biostudies-literatureHartz SMIntramural NIH HHSNCATS NIH HHSNIDA NIH HHSNIMH NIH HHSNCI NIH HHS77-84https://www.ebi.ac.uk/biostudies/studies/S-EPMC3107398biostudies-literatureUnknown21(2)OBJECTIVE:Owing to the clinical relationship between bipolar disorder and nicotine dependence, we investigated two research questions: (i) are genetic associations with nicotine dependence different in individuals with bipolar disorder as compared with individuals without bipolar disorder, and (ii) do loci earlier associated with nicotine dependence have pleiotropic effects on these two diseases. METHOD:Our study consisted of 916 cases with bipolar disorder and 1028 controls. On the basis of known associations with nicotine dependence, we genotyped eight single-nucleotide polymorphisms (SNPs) on chromosome 8 (three bins) in the regions of CHRNB3 and CHRNA6, and six SNPs on chromosome 15 (three bins) in the regions of CHRNA5 and CHRNA3. RESULTS:To determine whether the genetic associations with nicotine dependence are different in bipolar disorder than in the general population, we compared allele frequencies of candidate SNPs between individuals with nicotine dependence only and individuals with both nicotine dependence and bipolar disorder. There were no statistical differences between these frequencies, indicating that genetic association with nicotine dependence is similar in individuals with bipolar disorder as in the general population. In the investigation of pleiotropic effects of these SNPs on bipolar disorder, two highly correlated synonymous SNPs in CHRNB3, rs4952 and rs4953, were significantly associated with bipolar disorder (odds ratio 1.7, 95% confidence interval: 1.2-2.4, P=0.001). This association remained significant both after adjusting for a smoking covariate and analyzing the association in nonsmokers only. CONCLUSION:Our results suggest that (i) bipolar disorder does not modify the association between nicotine dependence and nicotinic receptor subunit genes, and (ii) variants in CHRNB3/CHRNA6 are independently associated with bipolar disorder.Psychiatric geneticsGenetic association of bipolar disorder with the ?(3) nicotinic receptor subunit gene.PMC3107398R01 MH59553R01 MH60068R01 MH059548R01 MH059545R01 MH059556R01 MH059534R01 MH059567R01 MH059535R01 MH059533R01 MH094483R01 MH060068R01 MH059553R01 MH59535R01 MH59545R01 MH59533K02 DA021237P50CA89392R01MH595675K02DA021237Z01 MH002810K02 DA21237P01 CA089392KL2 TR0004501Z01MH002810-01Rice JLin PCaserta MBowman ESGlitz DADetera-Wadleigh SBierut LMiller MJNwulia EZandi PPNurnberger JHipolito MKelsoe JSmiley CKravitz HMMurphy DLRochberg NNelson EForoud TVaughn-Brown AMeyer ETLawson WBBerrettini WXuei XSanders ADinwiddie SMcKinney RRice JPSamavedy NMacKinnon DFSaccone SReich TEdenberg HMondimore FMDick DMEdenberg HJBierut LJDePaulo JRAvramopoulos DMarta DGershon EEl-Mallakh RBederow LCrowe RHarakal DMcMahon FKassem LRau NLByerley WManji HFlury LCoryell WNguyen TVinogradov SBadner JScheftner WMcMahon FJHartz SMMcInnis MMoe PRAustin LPotash JBNIMH Genetics Initiative Bipolar Disorder ConsortiumGoate ALiu CPayne JfalseGenetic association of bipolar disorder with the ?(3) nicotinic receptor subunit gene.OBJECTIVE:Owing to the clinical relationship between bipolar disorder and nicotine dependence, we investigated two research questions: (i) are genetic associations with nicotine dependence different in individuals with bipolar disorder as compared with individuals without bipolar disorder, and (ii) do loci earlier associated with nicotine dependence have pleiotropic effects on these two diseases. METHOD:Our study consisted of 916 cases with bipolar disorder and 1028 controls. On the basis of known associations with nicotine dependence, we genotyped eight single-nucleotide polymorphisms (SNPs) on chromosome 8 (three bins) in the regions of CHRNB3 and CHRNA6, and six SNPs on chromosome 15 (three bins) in the regions of CHRNA5 and CHRNA3. RESULTS:To determine whether the genetic associations with nicotine dependence are different in bipolar disorder than in the general population, we compared allele frequencies of candidate SNPs between individuals with nicotine dependence only and individuals with both nicotine dependence and bipolar disorder. There were no statistical differences between these frequencies, indicating that genetic association with nicotine dependence is similar in individuals with bipolar disorder as in the general population. In the investigation of pleiotropic effects of these SNPs on bipolar disorder, two highly correlated synonymous SNPs in CHRNB3, rs4952 and rs4953, were significantly associated with bipolar disorder (odds ratio 1.7, 95% confidence interval: 1.2-2.4, P=0.001). This association remained significant both after adjusting for a smoking covariate and analyzing the association in nonsmokers only. CONCLUSION:Our results suggest that (i) bipolar disorder does not modify the association between nicotine dependence and nicotinic receptor subunit genes, and (ii) variants in CHRNB3/CHRNA6 are independently associated with bipolar disorder.2011-01-01T00:00:00Z2011 Apr2020-11-19T10:20:13Z2019-03-27T00:42:14ZS-EPMC31073982119131510.1097/ypg.0b013e32834135eb10.1097/YPG.0b013e32834135eb